Immune biomarkers and response to checkpoint inhibition of BRAF(V600) and BRAF non-V600 altered lung cancers Journal Article


Authors: Murciano-Goroff, Y. R.; Pak, T.; Mondaca, S.; Flynn, J. R.; Montecalvo, J.; Rekhtman, N.; Halpenny, D.; Plodkowski, A. J.; Wu, S. L.; Kris, M. G.; Paik, P. K.; Riely, G. J.; Yu, H. A.; Rudin, C. M.; Hellmann, M. D.; Land, J. D.; Buie, L. W.; Heller, G.; Lito, P.; Yaeger, R.; Drilon, A.; Liu, D.; Li, B. T.; Offin, M.
Article Title: Immune biomarkers and response to checkpoint inhibition of BRAF(V600) and BRAF non-V600 altered lung cancers
Abstract: Background While 2-4% of lung cancers possess alterations in BRAF, little is known about the immune responsiveness of these tumours. Methods Clinical and genomic data were collected from 5945 patients with lung cancers whose tumours underwent next-generation sequencing between 2015 and 2018. Patients were followed through 2020. Results In total, 127 patients with metastatic BRAF-altered lung cancers were identified: 29 tumours had Class I mutations, 59 had Class II/III alterations, and 39 had variants of unknown significance (VUS). Tumour mutation burden was higher in Class II/III than Class I-altered tumours (8.8 mutations/Mb versus 4.9, P < 0.001), but this difference was diminished when stratified by smoking status. The overall response rate to immune checkpoint inhibitors (ICI) was 9% in Class I-altered tumours and 26% in Class II/III (P = 0.25), with median time on treatment of 1.9 months in both groups. Among patients with Class I-III-altered tumours, 36-month HR for death in those who ever versus never received ICI was 1.82 (1.17-6.11). Nine patients were on ICI for >2 years (two with Class I mutations, two with Class II/III alterations, and five with VUS). Conclusions A subset of patients with BRAF-altered lung cancers achieved durable disease control on ICI. However, collectively no significant clinical benefit was seen.
Keywords: mutations; clinicopathological features; adenocarcinomas; multicenter; landscape; clinical characteristics; open-label; pembrolizumab; dabrafenib plus trametinib; mutant nsclc
Journal Title: British Journal of Cancer
Volume: 126
Issue: 6
ISSN: 0007-0920
Publisher: Nature Publishing Group  
Date Published: 2022-04-01
Start Page: 889
End Page: 898
Language: English
ACCESSION: WOS:000735340000002
DOI: 10.1038/s41416-021-01679-1
PROVIDER: wos
PMCID: PMC8927094
PUBMED: 34963703
Notes: Article -- Source: Wos
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MSK Authors
  1. Natasha Rekhtman
    434 Rekhtman
  2. Glenn Heller
    400 Heller
  3. Helena Alexandra Yu
    291 Yu
  4. Piro Lito
    58 Lito
  5. Gregory J Riely
    605 Riely
  6. Rona Denit Yaeger
    324 Yaeger
  7. Paul K Paik
    257 Paik
  8. Mark Kris
    872 Kris
  9. Alexander Edward Drilon
    637 Drilon
  10. Matthew David Hellmann
    412 Hellmann
  11. Charles Rudin
    495 Rudin
  12. Bob Tingkan Li
    279 Li
  13. Larry Wayne Buie
    25 Buie
  14. Josiah David Land
    7 Land
  15. Dazhi   Liu
    45 Liu
  16. Michael David Offin
    173 Offin
  17. Jessica Flynn
    182 Flynn
  18. Terry Kheng Pak
    12 Pak
  19. Stephanie Leann Wu
    4 Wu